TY - JOUR T1 - Induction of Apoptosis in Hematopoietic Cells with an Antibody Against Tomoregulin-1 JF - Anticancer Research JO - Anticancer Res SP - 339 LP - 346 VL - 26 IS - 1A AU - LOUIS C. PENNING AU - CHRISTINE J. PIEK AU - DOUG W. EIB AU - RAYMOND G. SCHIPPER AU - TJADINE M. HOLLING AU - GERARD J.M. MARTENS Y1 - 2006/01/01 UR - http://ar.iiarjournals.org/content/26/1A/339.abstract N2 - Tomoregulin-1, a type-I transmembrane protein with two follistatin modules, a unique epidermal growth factor (EGF) domain and a short, highly conserved cytoplasmic tail, was studied. A number of hematopoietic cell lines (L1210, CEM, Jurkat, U937, K562, JY, THP-1 and T2) express tomoregulin-1 endogenously. In these cells, apoptosis was induced by an antiserum (C29) and purified IgG against the follistatin modules, but not by antisera against the EGF-domain or the cytoplasmic tail. Furthermore, C29 induced apoptosis in tomoregulin-1-, but not in mock-transfected cells. Apoptosis was monitored through genomic DNA fragmentation, annexin-V staining and caspase-3 activation. Treatment of the cells with C29 in the presence of H89 (a Ser/Thr kinase inhibitor) or 8′-bromo-cyclicAMP revealed that apoptosis was mediated by a cAMP-dependent Ser/Thr kinase. Moreover, C29 increased [cAMP]i over 5-fold. Together, these data suggest that the C29 antiserum against tomoregulin-1 induces apoptosis of hematopoietic cells. Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -